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Vaginal cancer treated with curative radiotherapy with or without concomitant chemotherapy: oncologic outcomes and prognostic factors

Meixner, Eva; Arians, Nathalie; Bougatf, Nina; Hoeltgen, Line; König, Laila; Lang, Kristin; Domschke, Christoph; Wallwiener, Markus; Lischalk, Jonathan W; Kommoss, Felix K F; Debus, Jürgen; Hörner-Rieber, Juliane
BACKGROUND/UNASSIGNED:Vaginal cancer is a rare disease for which prospective randomized trials do not exist. We aimed to assess survival outcomes, patterns of recurrence, prognostic factors, and toxicity in the curative treatment using image-guided radiotherapy (RT). METHODS/UNASSIGNED:In this retrospective review, we identified 53 patients who were treated at a single center with external beam radiotherapy and brachytherapy with or without concomitant chemotherapy from 2000 to 2021. RESULTS/UNASSIGNED:= 0.027). Minimal toxicity was observed with no patients having documentation of high-grade toxicity (CTCAE grade 3+). CONCLUSION/UNASSIGNED:In treatment of vaginal cancer, high-dose RT in combination with brachytherapy is well tolerated and results in effective local control rates, which significantly improve with an EQD2(α/β=10) ⩾65 Gy. Multivariate analyses revealed concomitant chemotherapy was a positive prognostic factor for overall and progression-free survival.
PMID: 34724840
ISSN: 2038-2529
CID: 5037892

Association Between Travel Distance and Use of Postoperative Radiation Therapy for Incompletely Resected Non-Small Cell Lung Cancer

McGunigal, M; Singh, T; Amarell, K; Aghdam, N; Paudel, N; Lischalk, J W
PURPOSE/OBJECTIVE(S): Postoperative radiation (PORT) is recommended by consensus guidelines for incompletely resected stage II-III non-small cell lung cancer (NSCLC) to optimize local control. Prior data across disease sites has suggested disparities exist in receipt of beneficial adjuvant therapies based on sociodemographic barriers including geography. We sought to explore if receipt of PORT in margin positive locally advanced NSCLC was related to travel distance from the treating facility. MATERIALS/METHODS: We identified patients with pathologic stage II-III NSCLC within the National Cancer Data Base who underwent treatment with upfront surgery (lobectomy or pneumonectomy) found to have microscopic (R1) or macroscopic (R2) residual tumor. Only patients coded as receiving adjuvant external-beam PORT (50-74 Gy) or no radiation were included. Multivariable logistic regression was utilized to determine factors associated with PORT receipt. Cox regression was used to identify predictors of survival.
RESULT(S): We identified 7,270 pathologic stage II-III NSCLC patients who underwent R1/R2 resections from 2004-2015; of these, 36% received PORT. Median overall survival in these patients was significantly improved with the addition of PORT, from 22.3 months to 32.8 months and this persisted when stratified by distance traveled (see table 1). Of the patients who did not receive PORT, 43.4% did receive adjuvant chemotherapy and < 1% received immunotherapy. Reason for why PORT was not given was largely unknown, but stated reasons included: contraindicated due to risk factors (3.6%) and patient refusal (4.2%). In contrast, 79.1% of PORT patients also received chemotherapy. Half of PORT patients resided within 10 miles of treatment facility. Progressively father travel distance was associated with decreased likelihood of PORT (OR 0.89, P=0.002). Other factors associated with decreased PORT receipt included older age and decreased level of education. On Cox regression, higher co-morbidity score was predictive of death, while receipt of PORT was protective (HR 0.87, P < 0.001).
CONCLUSION(S): For NSCLC patients with margin positive disease after surgery, increasing distance was associated with decreased likelihood of receiving PORT, despite being routinely recommended in this setting and proven survival benefit irrespective of geography in our patient cohort. Decreased likelihood to receive PORT with increasing travel distance suggests location may play a role in the decision to undergo PORT for these patients with adverse pathology.
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EMBASE:636627141
ISSN: 1879-355x
CID: 5082142

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old

Haas, J A; Mendez, C; Katz, A; Witten, M R; Carpenter, T J; Repka, M C; Lischalk, J W; Oshinsky, G; Sanchez, A; Haas, D; Blacksburg, S R
PURPOSE/OBJECTIVE(S): Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. MATERIALS/METHODS: Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.
RESULT(S): At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.
CONCLUSION(S): This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.
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EMBASE:636626161
ISSN: 1879-355x
CID: 5082162

Stereotactic Body Radiation Therapy for Ultra-Large (> 100 cc) Prostate Glands: Oncologic, Toxicity and Patient-Reported Outcomes

Haas, J A; Mendez, C; Witten, M R; Katz, A; Carpenter, T J; Repka, M C; Lischalk, J W; Lepor, H; Sanchez, A; Haas, D; Blacksburg, S R
PURPOSE/OBJECTIVE(S): Historically, caution has been warranted when irradiating large target volumes particularly those in close proximity to organs at risk. Prior literature has demonstrated an increased incidence of GI and GU toxicity when men with large prostates were treated with conventionally fractionated radiation therapy. However, there is very limited data regarding the clinical outcomes when SBRT is used as a definitive treatment modality. We explore the long term oncologic, toxicity, and patient reported outcomes of men treated with definitive SBRT with ultra-large prostate glands (>= 100 cc.) MATERIALS/METHODS: From 2006 to 2020, a total of 3,393 patients with low and intermediate risk prostate cancer were treated with definitive robotic-SBRT. We performed a retrospective review to identify all patients in this cohort with pre-treatment prostate volumes >= 100 cc. Prostate volume was measured at the time of treatment regardless of ADT incorporation. All patients were treated to a total dose of 35-36.25 Gy in 5 fractions. All patients had a minimum of 2 years follow-up and were given pre- and post-treatment EPIC questionnaires at defined intervals. Biochemical control was assessed using the Phoenix definition. Late toxicity was defined using CTCAE version 5.0 and was characterized as occurring >= 6 months post treatment.
RESULT(S): A total of 67 patients were identified with >= 100 cc prostate glands. Of these, 18 patients received ADT prior to treatment. Overall, the median prostate volume was 139.37 cc (range 100.1 - 227 cc). The D'Amico risk classification was low (n=19) and intermediate (n=48). The median age was 70 years (range 54 - 87 years) and the median pretreatment PSA was 8.7 ng/ml. The mean pre-treatment EPIC bowel and urinary scores were 87.8 and 79.7, respectively. One-month following SBRT, mean EPIC bowel and urinary scores worsened to 83.6 and 76.5, respectively. Three months following SBRT, mean epic bowel and urinary scores continued to decline to 83.2 and 77.1, respectively. However, bowel and bladder symptomatology improved by 1 year to 86.16 and 77.19, and by 2 years improved above baseline to 90.00 and 85.78, respectively. There were no high grade (3+) GI toxicities observed, though one grade 3 urinary retention was identified. Excellent oncologic outcomes were observed with a 5-year median PSA nadir of 0.6 ng/mL and a biochemical relapse free survival (bRFS) of 100% at 5 years.
CONCLUSION(S): SBRT has been demonstrated to be oncologically effective with minimal toxicity, and has become a more ubiquitous radiation option in men with localized prostate cancer. Although there is a historical reticence for treatment of men with large glands, we report excellent clinical outcomes. Five-year bRFS was 100% and grade 3+ urinary toxicity was 2%. Although EPIC scores transiently dropped at 1 and 3 months following SBRT, resolution was seen by 1 year following treatment. The use of SBRT for the treatment of localized prostate cancer in men with ultra-large prostate gland is feasible with minimal toxicity.
Copyright
EMBASE:636626059
ISSN: 1879-355x
CID: 5082182

Predictors and Consequences of Refusing Recommended Radiation for Locally Advanced Inoperable Non-Small Cell Lung Cancer

McGunigal, M; Amarell, K; Singh, T; Chou, J; Aghdam, N; Paudel, N; Lischalk, J W
PURPOSE/OBJECTIVE(S): Definitive chemoradiation is standard-of-care treatment for locally advanced inoperable non-small cell lung cancer (NSCLC). However, some patients refuse radiation therapy (RT) and this information is captured in the National Cancer Database (NC
EMBASE:636624207
ISSN: 1879-355x
CID: 5082262

Radiolucent Carbon Fiber-Reinforced Implants for Treatment of Spinal Tumors-Clinical, Radiographic, and Dosimetric Considerations

Takayanagi, Ariel; Siddiqi, Imran; Ghanchi, Hammad; Lischalk, Jonathan; Vrionis, Frank; Ratliff, John; Bilsky, Mark; Hariri, Omid R
The management of spine tumors is multimodal and personalized to each individual patient. Patients often require radiation therapy after surgical fixation. Although titanium implants are used most commonly, they produce significant artifact, leading to decreased confidence in target-volume coverage and normal tissue sparing. Carbon-based materials have been found to have minimal effects on dose perturbation in postoperative radiation therapy and have shown biostability and biocompatibility that are comparable to titanium implants. Using the PubMed and Web of Sciences databases, we conducted a systematic review of carbon-based screw and rod fixation systems in the treatment of spinal tumors. We reviewed clinical studies regarding safety of spine fixation with carbon fiber-reinforced (CFR) implants and biomechanical studies, as well as radiation and dosimetric studies. The radiolucency of CFR-polyether ether ketone implants has the potential to benefit patients with spine tumor. Clinical studies have shown no increase in complications with implementation of CFR-polyether ether ketone implants, and these devices seem to have sufficient stiffness and pullout strength. However, further trials are necessary to determine if there is a clinically significant impact on local tumor control.
PMID: 34062294
ISSN: 1878-8769
CID: 5013492

Stereotactic body radiation therapy for the treatment of localized prostate cancer in men with underlying inflammatory bowel disease

Lischalk, Jonathan W; Blacksburg, Seth; Mendez, Christopher; Repka, Michael; Sanchez, Astrid; Carpenter, Todd; Witten, Matthew; Garbus, Jules E; Evans, Andrew; Collins, Sean P; Katz, Aaron; Haas, Jonathan
BACKGROUND:Historically, IBD has been thought to increase the underlying risk of radiation related toxicity in the treatment of prostate cancer. In the modern era, contemporary radiation planning and delivery may mitigate radiation-related toxicity in this theoretically high-risk cohort. This is the first manuscript to report clinical outcomes for men diagnosed with prostate cancer and underlying IBD curatively treated with stereotactic body radiation therapy (SBRT). METHODS:A large institutional database of patients (n = 4245) treated with SBRT for adenocarcinoma of the prostate was interrogated to identify patients who were diagnosed with underlying IBD prior to treatment. All patients were treated with SBRT over five treatment fractions using a robotic radiosurgical platform and fiducial tracking. Baseline IBD characteristics including IBD subtype, pre-SBRT IBD medications, and EPIC bowel questionnaires were reviewed for the IBD cohort. Acute and late toxicity was evaluated using the CTCAE version 5.0. RESULTS:A total of 31 patients were identified who had underlying IBD prior to SBRT for the curative treatment of prostate cancer. The majority (n = 18) were diagnosed with ulcerative colitis and were being treated with local steroid suppositories for IBD. No biochemical relapses were observed in the IBD cohort with early follow up. High-grade acute and late toxicities were rare (n = 1, grade 3 proctitis) with a median time to any GI toxicity of 22 months. Hemorrhoidal flare was the most common low-grade toxicity observed (n = 3). CONCLUSION/CONCLUSIONS:To date, this is one of the largest groups of patients with IBD treated safely and effectively with radiation for prostate cancer and the only review of patients treated with SBRT. Caution is warranted when delivering therapeutic radiation to patients with IBD, however modern radiation techniques appear to have mitigated the risk of GI side effects.
PMCID:8267228
PMID: 34243797
ISSN: 1748-717x
CID: 4965222

Thymic malignancies treated with active scanning proton beam radiation and Monte Carlo planning: early clinical experience [Letter]

McGunigal, Mary; Margolis, Marc; Forsthoefel, Matthew; Singh, Tanvee; Amarell, Katherine; Deblois, David; Campbell, Lloyd; Kim, Chul; Liu, Stephen; Bergquist, Peter J; Debrito, Pedro; Collins, Brian T; Giaccone, Giuseppe; Lischalk, Jonathan W
PMID: 33629926
ISSN: 1651-226x
CID: 5013462

Intensity Modulated Radiation Therapy (IMRT) With Simultaneously Integrated Boost Shortens Treatment Time and Is Noninferior to Conventional Radiation Therapy Followed by Sequential Boost in Adjuvant Breast Cancer Treatment: Results of a Large Randomized Phase III Trial (IMRT-MC2 Trial)

Hörner-Rieber, Juliane; Forster, Tobias; Hommertgen, Adriane; Haefner, Matthias F; Arians, Nathalie; König, Laila; Harrabi, Semi B; Schlampp, Ingmar; Weykamp, Fabian; Lischalk, Jonathan W; Heinrich, Vanessa; Weidner, Nicola; Hüsing, Johannes; Sohn, Christof; Heil, Jörrg; Hof, Holger; Krug, David; Debus, Jürgen
PURPOSE:In the modern era, improvements in radiation therapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiation therapy after breast conservation surgery. Nevertheless, randomized trials supporting the noninferiority of this treatment to historical standards of care approach are lacking. METHODS:A prospective, multicenter, randomized phase 3 trial (NCT01322854) was performed to analyze noninferiority of conventional fractionated intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) to 3-D conformal radiation therapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (noninferiority margin at hazard ratio [HR] of 3.5) as well as cosmetic results 6 weeks and 2 years after radiation therapy (evaluated via photo documentation calculating the relative breast retraction assessment [pBRA] score [noninferiority margin of 1.25]). RESULTS:A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was noninferior to the 3-D-CRT-seqB arm (99.6% vs 99.6%, respectively; HR, 0.602; 95% CI, 0.123-2.452; P = .487). In addition, noninferiority was also shown for cosmesis after IMRT-SIB and 3-D-CRT-seqB at both 6 weeks (median pBRA, 9.1% vs 9.1%) and 2 years (median pBRA, 10.4% vs 9.8%) after radiation therapy (95% CI, -0.317 to 0.107 %; P = .332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late-toxicity evaluation with the late effects normal tissues- subjective, objective, management, analytic criteria, a score for the evaluation of long-term adverse effects in normal tissue, revealed no significant differences between treatment arms. In addition, there was no difference in overall survival rates (99.6% vs 99.6%; HR, 3.281; 95% CI: -0.748 to 22.585; P = .148) for IMRT-SIB and 3-D-CRT-seqB, respectively. CONCLUSIONS:To our knowledge, this is the first prospective trial reporting the noninferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow-up. This treatment regimen considerably shortens adjuvant radiation therapy times without compromising clinical outcomes.
PMID: 33321192
ISSN: 1879-355x
CID: 5013422

Radiation Modalities Used in Lung Cancer: An Overview for Thoracic Surgeons

McGunigal, Mary; Lischalk, Jonathan W; Randolph-Jackson, Pamela; Khaitan, Puja Gaur
Radiation is a constantly evolving technology which plays a role in the management of lung cancer in a variety of settings: as an adjunct to surgery, definitively, and palliatively. Key aspects of radiation oncology-including acute and chronic toxicities of thoracic radiation and rationale for choosing one modality of radiation over another-may be obscure to those outside the field. We aim to provide a useful overview relevant for the thoracic surgeon of radiation technology and delivery. A review was performed of salient articles identifying radiation technologies used in lung cancer which were summarized and expounded upon with focus on integrating their history, evolution, and landmark trials establishing basis of their use. This article reviews the four fundamental means of external beam radiation employed in managing lung cancer and provides visual examples of comparison plans. We also touch on potential practice-changing developments in regards to proton therapy and radiation in the era of immunotherapy. Radiation oncology has evolved considerably over time to become a critical part of lung cancer management, particularly in early-stage inoperable disease and locally advanced disease. Maximizing tumor control while minimizing toxicity drives treatment strategies. Knowledge of these fundamentals will help the thoracic surgeon answer many questions patients pose regarding radiation.
PMID: 33705939
ISSN: 1532-9488
CID: 5013472